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NATIONAL INSTITUTE FOR HEALTH AND CARE
EXCELLENCE
Medical technology guidance
SCOPE
Spectra Optia Apheresis System for automated red
blood cell exchange in patients with sickle cell
disease
1
Technology
1.1
Description of the technology
The Spectra Optia Apheresis System (Terumo) is used for automated red
blood cell depletion and exchange in adults or children with sickle cell disease
who are on a long term or temporary/medium-term transfusion regime.
The system comprises 3 components: the apheresis machine; embedded
software; and a single-use disposable blood tubing set. Venous access for the
Spectra Optia Apheresis System is usually through an arm or large leg vein.
The latter is a more complicated procedure that requires additional expertise,
often involving vascular radiologists. Following removal of blood from the
patient, the constituent components are separated by the Spectra Optia
Apheresis System using continuous flow and centrifugation. A patented
optical detection technology (known as automated interface management)
monitors the position and thickness of the blood components and feeds this
information to the selected device protocol which can adjust appropriate
pumps and valves in real time to efficiently remove targeted components. The
device protocol, software and automated interface management system
facilitates replacing the removed fractions with donor red blood cells and fluid
as required. The procedure typically takes 2–3 hours.
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
The Spectra Optia Apheresis System should be operated by trained
healthcare professionals. The system may be used in a specialist day-care
setting and, if the patient is well enough, they may return to normal activities
immediately after the procedure.
1.2
Regulatory status
The Spectra Optia Apheresis System has a CE mark as a class IIb medical
device for the design, development and manufacture of blood cell separators.
It first received a CE mark in 2007.
The device may also be used to perform mononuclear cell collection,
collection of donor lymphocytes and haematopoietic progenitor cells, white
blood cell depletion, bone marrow processing, platelet depletion,
polymorphonuclear cell (including granulocyte) collections and plasma
exchange. These uses are outside the scope of this evaluation.
1.3
Claimed benefits
The benefits to patients claimed by the company are:
 Automated red blood cell exchange using the Spectra Optia Apheresis
System has a longer clinical effect than manual red blood cell exchange
meaning that patients would require treatment only every 6–8 weeks in
comparison with every 3–4 weeks.
 Automated red blood cell exchange with this device is faster than manual
red blood cell exchange with treatment lasting approximately 2–3 hours in
comparison to 4–8 hours. This makes the procedure more convenient for
patients which may improve compliance.
 Treatment with the Spectra Optia Apheresis System could allow patients to
reduce or cease iron chelation treatment due to reduced iron overloading.
This medication can cause significant side effects which may lead to poor
compliance.
 Increased patient compliance and efficiency of automated red blood cell
exchange, in comparison with other transfusion methods could improve
disease outcomes for patients. These improved outcomes include: reduced
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
incidence of stroke, reduced frequency and severity of pain crises, reduced
incidence of acute chest syndrome, improved outcomes following surgery,
and increased body mass index and growth in paediatric patients as well as
improved general quality of life.
The benefits to the healthcare system claimed by the company are:
 The Spectra Optia Apheresis System maintains haematocrit levels which
prevents iron overloading. This allows for the reduction or cessation of
treatment (within 12–18 months, depending on the severity of iron
overloading) with high cost, infusion-pump administered iron chelator
desferrioxamine or oral chelators such as deferasirox and deferiprone.
 Reduced hospital stay and staff time are needed as automated red blood
cell exchange can be performed by a trained nurse, is faster (2–3 hours for
6–8units), and allows for an increased interval between treatments (every
6–8 weeks). During manual red blood cell exchange, doctors are required
to estimate haematocrit levels so that each unit of blood drawn off is
replaced by the correct volume of packed red blood cells. This procedure
can last for between 6 hours (3–4 units exchanged) and 2 days (8 units
exchanged) depending on the patient’s sickle haemoglobin (HbS) levels.
Manual red blood cell exchange should be repeated every 3–4 weeks.
 Reduced complications from sickle cell disease leading to reduced
hospitalisations and associated treatment.
 The depletion-exchange protocol of the machine makes better use of donor
blood as only the required fraction is used allowing the remaining blood
components to be used in other patients.
1.4
Relevant diseases and conditions
Patients with sickle cell disease have a mutated variant of haemoglobin that
causes red blood cells to form a distinctive sickle shape. These red blood cells
do not flow easily and can cause blockages, known as vaso-occlusive crises.
This can occur in any part of the body but is most serious when it restricts the
blood flow to major organ systems.
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
While serious organ damage is a concern, all vaso-occlusive events are
extremely painful for the patient and will often require emergency admission to
hospital and pain management with opiates. These acute episodes of extreme
pain are likely to have a negative impact on the person’s work or school and
daily life. More serious complications such as stroke and acute chest
syndrome can lead to significant morbidity and a reduced life expectancy.
In England, there are an estimated 240,000 carriers of the sickle cell trait and
around 13,500 people with sickle cell disease. Sickle cell disease is the most
common serious genetic disorder in England and affects 1 in 2000 live births,
or 350 babies a year. People with sickle cell disease tend to live in urban
areas where birth prevalence may be as high as 1 in 300. However, the NHS
Sickle Cell & Thalassaemia Screening Programme has identified affected
infants in all parts of the country. Sickle cell disease is most common in
people whose families originate from Africa, the Caribbean, the Eastern
Mediterranean, the Middle East and Asia. In the UK the majority of people
with sickle cell disease are of African and Caribbean descent. In this
population, at least 1 in 10–40 people carry the sickle cell trait and 1 in 60–
200 has sickle cell disease. Around 10–20% of patients with sickle cell
disease require regular blood transfusions or red blood cell exchange.
1.5
Current management
The most commonly available current management involves replacing sickled
red blood cells with healthy red blood cells or drug therapy or a combination of
both, with the aim of lessening symptoms and long-term complications. The
type of treatment delivered depends on the severity of symptoms and will
always be planned in order to minimise the risk of further complications. The
range of treatment is similar for adults and children with sickle cell disease
although the order in which they are given may vary. Both adults and children
with sickle cell disease are more susceptible to infections and antibiotic
prophylaxis and immunisations are routinely recommended for children who
are not contra-indicated. NICE has produced a guideline on the management
of an acute painful sickle cell episode in hospital. NHS Sickle Cell and
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
Thalassemia Screening Programme has also produced Sickle cell disease in
childhood, standards and guidelines for clinical care.
The chemotherapy drug hydroxycarbamide may be prescribed since it
stimulates the production of fetal haemoglobin which is unaffected by the
sickle cell mutation. However, this drug may be ineffective in up to 25% of
patients, often causes serious side effects and cannot be taken by either men
or women prior to conception or by women during pregnancy or
breastfeeding. If hydroxycarbamide is ineffective, contra-indicated or
associated with side effects, the patient may require a long-term red blood cell
transfusion regime.
Automated or manual red blood cell exchange in sickle cell disease is used in
the treatment of acute sickle cell complications or to prevent long-term
complications by reducing the proportion of sickle cell haemoglobin (HbS)
cells in circulation. For example, patients with sickle cell disease may require
red cell exchange for stroke prevention (most commonly used in children with
sickle cell disease who are identified as being at a high risk of stroke after
transcranial Doppler investigations), established or threatened organ failure
and acute chest syndrome. A temporary blood transfusion regime may be set
up for patients with leg ulcers or for those discontinuing hydroxycarbamide
prior to conception or pregnancy.
If donor red blood cells are given in a blood transfusion, the haematocrit
(percentage of the volume of whole blood that is made up of red blood cells)
may increase above 30% which increases the risk of hyperviscosity and vasoocclusive events. Increased haematocrit levels can also lead to iron overload,
which can lead to important clinical consequences. As there is no mechanism
for the body to remove the extra iron from transfused red blood cells it
accumulates in the liver, heart and other organs. If left untreated this excess
iron can cause organ damage, liver and heart failure, along with type II
diabetes. Iron overloading is a complex clinical problem which is very difficult
to treat. Iron chelation therapy is used to treat iron overload but these drugs
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
can cause unpleasant side effects and may need to be administered via an
overnight infusion pump.
Red blood cell exchange, automated or manual, can produce a significant
reduction in HbS (target usually <30%) thereby reducing the risk of
hyperviscosity or iron overload. Venous access can be problematic in patients
requiring regular or recurrent treatment.
Manual red blood cell exchange involves removing whole blood and infusing
the patient intravenously with donor red cells, to replace the sickle cells. This
method is time-consuming and it may not be possible to achieve the desired
reduction in HbS% in one procedure. It is usual that 3-4 units of blood will be
necessary, with the exchange of each unit lasting 2-4 hours. This treatment
needs to be repeated every 3-4 weeks. It should also be noted that managing
iron overloading during manual red blood cell exchange is very difficult and
usually requires the patient to be on chelation therapy. Chelation therapy is
administered orally or through an infusion pump and causes significant side
effects such as hepatic dysfunction, gastrointestinal disturbance, fever,
headache and injection site reactions. The severity of these side effects may
lead to low compliance in some patients leading to more serious iron-overload
complications such as an increased risk of heart failure, liver or spleen
enlargement and death due to toxicity.
All transfusion therapies for patients with sickle cell anaemia carry a risk of
alloimmunisation which occurs in approximately 18% of patients and may
result in them not being able to receive certain types of blood.
Alloimmunisation is common as the majority of donor red blood cells in the UK
come from white Europeans.
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
2
Reasons for developing guidance on the
Spectra Optia Apheresis System for sickle cell
disease
The Committee considered that Spectra Optia may offer benefits to some
patients with sickle cell disease through an improvement in morbidity and
clinical outcomes. These benefits include a possible reduced length of
treatment, increased treatment interval, improved control of sickle cell
concentration and reduced iron overload, in comparison with manual red
blood cell exchanges and top-up transfusions.
The Committee considered that the replacement of manual red blood cell
exchange with Spectra Optia could result in cost savings for the healthcare
system arising from a reduced need for iron chelation therapy.
The Committee noted that development of medical technology guidance on
this device, if it is positive, may help promote wider adoption and better
access for patients.
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
3
Statement of the decision problem
Draft scope issued by NICE
Population
Intervention
Comparator(s)
Outcomes
Cost analysis
Subgroups to
be considered
Special
Sickle cell disease patients requiring a medium or long-term
exchange transfusion regime.
Spectra Optia Apheresis System
Manual red blood cell exchange
The outcome measures to consider include:
Primary outcomes
 Percentage of total haemoglobin that is HbS (HbS%), relative to
target percentage (usually <30%)
 Duration of exchange procedure
 Frequency of treatment
 Patient haematocrit (measure relative to prescribed target for
therapy)
 Iron overload and requirement for chelation therapy
 Clinical outcomes including frequency of stroke, multi-organ
failure, acute chest syndrome and pain crises
 Quality of life
 Length of hospital stay
 Staff time and staff group/grade
 Frequency of top-up transfusion required to treat sickle cell
complications
Secondary outcomes
 Ease of venous access, bruising and haematoma
 Device-related adverse events
 Hospital admissions
 Donor blood usage
 BMI and growth in children
Comparator(s): Manual red blood cell exchange
Costs will be considered from an NHS and personal social services
perspective.
The time horizon for the cost analysis will be sufficiently long to
reflect any differences in costs and consequences between the
technologies being compared.
Sensitivity analysis will be undertaken to address uncertainties in the
model parameters, which will include scenarios in which different
numbers and combinations of devices are needed.
 Children and adults at high risk of stroke
 Pregnant or breastfeeding women
 Patients with iron overload
 Patients with acute chest syndrome
 Patients with multi-organ failure
 Children
Sickle cell disease can have a substantial and long-term adverse
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
considerations,
including those
related to
equality
Special
considerations,
specifically
related to
equality issues
effect on the ability to carry out normal day-to-day activities, and as
such many people with sickle cell disease will be considered to be
disabled, a protected characteristic under the Equality Act, 2010.
Some religious groups, for example Jehovah’s Witnesses, are
opposed to blood transfusions. Religion and belief is a protected
characteristic under the Equality Act, 2010.
The majority of people with sickle cell disease in the UK are of black
African or Caribbean family origin.
There is currently an inequity of access to the highest standards of
care for sickle cell disease as treatments are only available in certain
cities in the UK.
Are there any people with a protected characteristic for
No
whom this device has a particularly disadvantageous
impact or for whom this device will have a
disproportionate impact on daily living, compared with
people without that protected characteristics?
Are there any changes that need to be considered in the
No
scope to eliminate unlawful discrimination and to promote
equality?
Is there anything specific that needs to be done now to
No
ensure MTAC will have relevant information to consider
equality issues when developing guidance?
Delete as appropriate, if yes please provide further details here:
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
Related NICE guidance
4
Published
 Sickle cell acute painful episode: Management of an acute painful sickle
cell episode in hospital. NICE clinical guideline 143 (2012). Available from
www.nice.org.uk/guidance/CG143
 Antenatal care. NICE clinical guideline 62 (2008). Available from
www.nice.org.uk/guidance/CG62
Under development
NICE is developing the following guidance (details available from
www.nice.org.uk):
 There is no related guidance under development.
5
External organisations
5.1
Professional organisations
5.1.1
Professional organisations contacted for expert advice
At the selection stage, the following societies were contacted for expert
clinical and technical advice:
 British Society of Haematology
 Clinical Reference Group for Haemoglobinopathy
 Royal College of Pathologists
 Rare Disease UK
 UK Forum on Haemoglobin Disorders
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015
5.1.2
Professional organisations invited to comment on the
draft scope
The following societies have been alerted to the availability of the draft scope
for comment:
 Rare Disease UK
 Royal College of Pathologists
 The British Society for Haematology
 UK Forum on Haemoglobin Disorders
5.2
Patient organisations
At the selection stage, NICE’s Public Involvement Programme contacted the
following organisations for patient commentary and alerted them to the
availability of the draft scope for comment:
 Action for Sick Children
 African Caribbean Leukaemia Trust
 Bliss
 Different Strokes
 Ethnic Health Foundation
 National Childbirth Trust
 Sickle Cell and Young Stroke Survivors
 Sickle Cell Society
 Specialised Healthcare Alliance
 Stroke Association
 Together for Short Lives
 Tommy's
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NICE medical technology scope: Spectra Optia Apheresis System for automated red blood
cell exchange in patients with sickle cell disease
Date: June 2015